Drugs List

Therapeutic Indications

Uses

Hormone replacement therapy for the treatment of the climacteric syndrome
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Contraindications

Major surgery with prolonged post-operative immobilisation
Abnormal liver function test
Breastfeeding
Cerebrovascular accident
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
Galactosaemia
Hepatic neoplasm
History of thromboembolic disorder
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Pulmonary embolism
Severe arterial disorder
Thromboembolic disorder
Thrombophilia
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Body mass index above 30kg per square metre
Family history of breast cancer
Family history of thromboembolic disorder
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Risk factor for oestrogen-dependent neoplasm
Severe headache
Asthma
Breast nodules
Cardiac impairment
Chloasma
Cholelithiasis
Coagulopathy
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Epileptic disorder
Fibrocystic breast disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary angioneurotic oedema
History of breast nodules
History of chloasma
History of depression
History of endometriosis
History of fibrocystic breast disorder
History of jaundice
History of otosclerosis
Hypertension
Hypertriglyceridaemia
Hypophyseal neoplasm
Lactose intolerance
Malignant neoplasm
Migraine
Otosclerosis
Renal impairment
Systemic lupus erythematosus
Uterine fibroids

Assess family medical history prior to commencing treatment
Exclude oestrogen dependent neoplasm before treatment
Pre-treatment medical history and clinical examination
Contains lactose
Resume use only after 2wks full ambulation from surgery/immobilisation
Do breast & pelvic exam. before & during treatment if clinically indicated
Abnormal and/or irregular bleeding should be investigated
Monitor blood glucose closely in patients with diabetes mellitus
Monitor hepatic function in patients with history of hepatic disease
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient that changes in their breasts should be reported to Dr/nurse
Increased risk of VTE during travel involving >5hr immobilisation
Combined HRT therapy may prevent radiological detection of breast cancer
May affect results of some laboratory tests
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if cholestasis develops
Discontinue if epilepsy is exacerbated
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if first occurrence or worsening of visual disturbances
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if headache associated with sudden dysphasia or vertigo occurs
Discontinue if headache associated with sudden motor disturbances occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if severe pain in the calf of one leg occurs
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden breathlessness (or cough with blood stained sputum)
Discontinue if sudden occurrence of visual/hearing/perceptual disorders
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach occurs
Discontinue if symptoms due to endometriosis are exacerbated
Advise patient not to take St John's wort concurrently
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT
Women with a history of chloasma should avoid exposure to sun/UV light

For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Developmental changes in the psychosexual performance of boys have been attributed to in utero exposure to estradiol and progesterone. Hormone exposed males demonstrated a trend to have less heterosexual experience and fewer masculine interests than controls. The use of estrogenic hormones during pregnancy is contraindicated.

Medroxyprogesterone demonstrates dose-related teratogenicity and toxicity in animals. Although the hormone is contraindicated in human pregnancy, inadvertent exposure to therapeutic dose does not appear to represent a significant risk of structural defects. Foetal growth retardation might be a low risk complication if administered within 4 weeks of conception.

The accidental administration of high-dose preparations has no risk-based reason for a termination of pregnancy. In the case of repeated high-dose administration, at least, a details ultrasound examination could verify a normal morphologic development of the foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Hormone replacement therapy is contraindicated during lactation.

There is limited information on the use of estradiol during breastfeeding but is capable of transfer into breast milk. The amount of milk produced can decrease as a result of the influence of estrogens.

Medroxyprogesterone studies indicate that concerns about immediate adverse effects on the infant is unfounded, however there is no data on the effects of progesterone on brain and liver development at this age. There is little or no effect on the milk supply and only a very limited effect on the composition.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

"Spotting" bleeding
Abdominal cramps
Aggravation of porphyria
Allergic skin reactions
Altered glucose tolerance
Bloating
Breakthrough bleeding
Breast enlargement
Breast tenderness
Changes in libido
Chloasma
Cholestatic jaundice
Dementia
Depression
Dizziness
Dysmenorrhoea
Endometrial hyperplasia
Erythema multiforme
Erythema nodosum
Exacerbation of angioedema
Fluid retention
Gallbladder disease
Headache
Increase in plasma triglyceride concentration
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased size of uterine fibroids
Intolerance to contact lenses
Ischaemic stroke
Itching
Leg cramps
Melasma
Menorrhagia
Migraine
Mood changes
Myocardial infarction
Nausea
Oedema
Pancreatitis
Premenstrual-like syndrome
Sodium retention
Tiredness
Visual disturbances
Vomiting
Weight changes

Presentation

Tablets containing estradiol valerate
Tablets containing estradiol valerate with medroxyprogesterone acetate
Tablets containing a placebo

Drugs List

Therapeutic Indications

Uses

Hormone replacement therapy for the treatment of the climacteric syndrome
Secondary prophylaxis of postmenopausal osteoporosis where risk of fracture

Dosage

Adults

Elderly

Contraindications

Major surgery with prolonged post-operative immobilisation
Abnormal liver function test
Breastfeeding
Cerebrovascular accident
Deep vein thrombosis
Familial conjugated hyperbilirubinaemias
Galactosaemia
Hepatic neoplasm
History of thromboembolic disorder
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Pulmonary embolism
Severe arterial disorder
Thromboembolic disorder
Thrombophilia
Uncontrolled endometrial hyperplasia
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Body mass index above 30kg per square metre
Family history of breast cancer
Family history of thromboembolic disorder
History of recurrent spontaneous abortion
Patients over 65 years
Predisposition to thromboembolic disease
Risk factor for oestrogen-dependent neoplasm
Severe headache
Asthma
Breast nodules
Cardiac impairment
Chloasma
Cholelithiasis
Coagulopathy
Diabetes mellitus
Endometrial hyperplasia
Endometriosis
Epileptic disorder
Fibrocystic breast disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary angioneurotic oedema
History of breast nodules
History of chloasma
History of depression
History of endometriosis
History of fibrocystic breast disorder
History of jaundice
History of otosclerosis
Hypertension
Hypertriglyceridaemia
Hypophyseal neoplasm
Lactose intolerance
Malignant neoplasm
Migraine
Otosclerosis
Renal impairment
Systemic lupus erythematosus
Uterine fibroids

Assess family medical history prior to commencing treatment
Exclude oestrogen dependent neoplasm before treatment
Pre-treatment medical history and clinical examination
Contains lactose
Resume use only after 2wks full ambulation from surgery/immobilisation
Do breast & pelvic exam. before & during treatment if clinically indicated
Abnormal and/or irregular bleeding should be investigated
Monitor blood glucose closely in patients with diabetes mellitus
Monitor hepatic function in patients with history of hepatic disease
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient that changes in their breasts should be reported to Dr/nurse
Increased risk of VTE during travel involving >5hr immobilisation
Combined HRT therapy may prevent radiological detection of breast cancer
May affect results of some laboratory tests
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if cholestasis develops
Discontinue if epilepsy is exacerbated
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if first occurrence or worsening of visual disturbances
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if headache associated with sudden dysphasia or vertigo occurs
Discontinue if headache associated with sudden motor disturbances occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if severe pain in the calf of one leg occurs
Discontinue if significant rise in blood pressure occurs
Discontinue if sudden breathlessness (or cough with blood stained sputum)
Discontinue if sudden occurrence of visual/hearing/perceptual disorders
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach occurs
Discontinue if symptoms due to endometriosis are exacerbated
Advise patient not to take St John's wort concurrently
Female: Not for contraception.Use non-hormonal contraception, if required
Advise patient of increased risk of breast cancer vs benefits of HRT
Women with a history of chloasma should avoid exposure to sun/UV light

For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.

Pregnancy and Lactation

Pregnancy

Hormone replacement therapy is contraindicated during pregnancy.

Developmental changes in the psychosexual performance of boys have been attributed to in utero exposure to estradiol and progesterone. Hormone exposed males demonstrated a trend to have less heterosexual experience and fewer masculine interests than controls. The use of estrogenic hormones during pregnancy is contraindicated.

Medroxyprogesterone demonstrates dose-related teratogenicity and toxicity in animals. Although the hormone is contraindicated in human pregnancy, inadvertent exposure to therapeutic dose does not appear to represent a significant risk of structural defects. Foetal growth retardation might be a low risk complication if administered within 4 weeks of conception.

The accidental administration of high-dose preparations has no risk-based reason for a termination of pregnancy. In the case of repeated high-dose administration, at least, a details ultrasound examination could verify a normal morphologic development of the foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Hormone replacement therapy is contraindicated during lactation.

There is limited information on the use of estradiol during breastfeeding but is capable of transfer into breast milk. The amount of milk produced can decrease as a result of the influence of estrogens.

Medroxyprogesterone studies indicate that concerns about immediate adverse effects on the infant is unfounded, however there is no data on the effects of progesterone on brain and liver development at this age. There is little or no effect on the milk supply and only a very limited effect on the composition.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Encourage patients to participate in the national breast cancer screening programme and the national cervical cancer screening programme as appropriate for their age. Breast awareness should also be encouraged and patients advised to report any changes in their breasts to their doctor or nurse

Advise patients to contact their doctor if they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

If patient has forgotten to take one tablet, the forgotten tablet should be taken within 12 hours or otherwise discarded. Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

Advise patient to seek advice at the first indications of pregnancy.

Advise patient of increased risk of breast cancer versus the benefits of HRT.

Side Effects

"Spotting" bleeding
Abdominal cramps
Aggravation of porphyria
Allergic skin reactions
Altered glucose tolerance
Bloating
Breakthrough bleeding
Breast enlargement
Breast tenderness
Changes in libido
Chloasma
Cholestatic jaundice
Dementia
Depression
Dizziness
Dysmenorrhoea
Endometrial hyperplasia
Erythema multiforme
Erythema nodosum
Exacerbation of angioedema
Fluid retention
Gallbladder disease
Headache
Increase in plasma triglyceride concentration
Increased risk of breast cancer
Increased risk of endometrial cancer
Increased size of uterine fibroids
Intolerance to contact lenses
Ischaemic stroke
Itching
Leg cramps
Melasma
Menorrhagia
Migraine
Mood changes
Myocardial infarction
Nausea
Oedema
Pancreatitis
Premenstrual-like syndrome
Sodium retention
Tiredness
Visual disturbances
Vomiting
Weight changes

Effects on Laboratory Tests

The use of oestrogen-progestogen combinations may affect clinical laboratory results. There may be an increase in serum transaminases, alkaline phosphatase, gamma-glutamyltransferase, bilirubin and binding proteins. Thyroid-binding globulin may rise leading to erroneous results in thyroid function tests.

HRT, especially oestrogen - progestogen combined therapy, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: December 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.

Summary of Product Characteristics: Tridestra. Orion Pharma (UK) Limited. Revised November 2021.

The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.org
Last accessed: 02 December 2015

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Estradiol. Last revised: 02 June 2015
Last accessed: 02 December 2015

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Medroxyprogesterone. Last revised: 01 October 2015
Last accessed: 02 December 2015